1887

Abstract

The dose–response of cattle exposed to the bovine spongiform encephalopathy (BSE) agent is an important component of modelling exposure risks for animals and humans and thereby, the modulation of surveillance and control strategies for BSE. In two experiments calves were dosed orally with a range of amounts of a pool of brainstems from BSE-affected cattle. Infectivity in the pool was determined by end-point titration in mice. Recipient cattle were monitored for clinical disease and, from the incidence of pathologically confirmed cases and their incubation periods (IPs), the attack rate and IP distribution according to dose were estimated. The dose at which 50 % of cattle would be clinically affected was estimated at 0.20 g brain material used in the experiment, with 95 % confidence intervals of 0.04–1.00 g. The IP was highly variable across all dose groups and followed a log-normal distribution, with decreasing mean as dose increased. There was no evidence of a threshold dose at which the probability of infection became vanishingly small, with 1/15 (7 %) of animals affected at the lowest dose (1 mg).

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82421-0
2007-04-01
2024-12-04
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/4/1363.html?itemId=/content/journal/jgv/10.1099/vir.0.82421-0&mimeType=html&fmt=ahah

References

  1. Arnold M. E., Wilesmith J. W. 2004; The age-dependent risk of infection to BSE of dairy cattle in Great Britain. Prev Vet Med 66:35–47 [CrossRef]
    [Google Scholar]
  2. Austin A. R., Hawkins S. A. C., Kelay N. S., Simmons M. M. 1994; New observations on the clinical signs of BSE and scrapie. In A Consultation on BSE with the Scientific Veterinary Committee of the Commission of the European Communities, held in Brussels 14–15 September 1993 pp 277–287 Edited by Bradley R., Marchant B. Document VI/4131/94-EN European Commission; Brussels:
    [Google Scholar]
  3. Austin A. R., Simmons M. M., Wells G. A. H. 1997; Pathological temperament changes in bovine animals. Bovine Pract 31:99–103
    [Google Scholar]
  4. Braun U., Pusterla N., Schicker E. 1998; Bovine spongiform encephalopathy: diagnostic approach and clinical findings. Compend Contin Educ Pract Vet 20, (Suppl.):5270–5278
    [Google Scholar]
  5. Bruce M., Chree A., McConnell I., Foster J., Pearson G., Fraser H. 1994; Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Philos Trans R Soc Lond B Biol Sci 343:405–411 [CrossRef]
    [Google Scholar]
  6. Buschmann A., Groschup M. H. 2005; Highly BSE sensitive transgenic mice confirm essential restriction of infectivity to the nervous system in clinically diseased cattle. J Infect Dis 192:934–942 [CrossRef]
    [Google Scholar]
  7. Casalone C., Caramelli M., Cresio M. I., Spencer Y. I., Simmons M. M. 2006; BSE immunohistochemical patterns in the brainstem: a comparison between UK and Italian cases. Acta Neuropathol (Berl) 111:444–449 [CrossRef]
    [Google Scholar]
  8. Cooley W. A., Clark J. K., Ryder S. J., Davis L. A., Farrelly S. S. J., Stack M. J. 2001; Evaluation of a rapid Western immunoblotting procedure of the diagnosis of bovine spongiform encephalopathy (BSE) in the UK. J Comp Pathol 125:64–70 [CrossRef]
    [Google Scholar]
  9. Dawson M., Wells G. A. H., Parker B. N. J. 1990; Preliminary evidence of the experimental transmissibility of bovine spongiform encephalopathy to cattle. Vet Rec 126:112–113
    [Google Scholar]
  10. Dell'Omo G., Vannoni E., Vyssotski A. L., Di Bari M. A., Nonno R., Agrimi U., Lipp H.-P. 2002; Early behavioural changes in mice infected with BSE and scrapie: automated home cage monitoring reveals prion strain differences. Eur J Neurosci 16:735–742 [CrossRef]
    [Google Scholar]
  11. Dickinson A. G., Meikle M. H., Fraser H. 1968; Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. J Comp Pathol 78:293–299 [CrossRef]
    [Google Scholar]
  12. Diringer H., Roehmel J., Beekes M. 1998; Effect of repeated oral infection of hamsters with scrapie. J Gen Virol 79:609–612
    [Google Scholar]
  13. EFSA 2005; Quantitative assessment of the residual BSE risk in bovine-derived products. EFSA QRA report 2004, working document EFSA J 307:1–135 http://www.efsa.eu.int/science/biohaz/biohaz_documents/1280/efsaqrareport2004_final20dec051.pdf
    [Google Scholar]
  14. Fieller E. C. 1940; The biological standardization of insulin. J R Stat Soc Ser A 7, (Suppl.):1–64
    [Google Scholar]
  15. Fraser H., Bruce M. E., Chree A., McConnell I., Wells G. A. H. 1992; Transmission of bovine spongiform encephalopathy and scrapie to mice. J Gen Virol 73:1891–1897 [CrossRef]
    [Google Scholar]
  16. Goldmann W., Hunter N., Martin T., Dawson M., Hope J. 1991; Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon. J Gen Virol 72:201–204 [CrossRef]
    [Google Scholar]
  17. Grassi J., Comoy E., Simon S., Creminon C., Frobert Y., Trapmann S., Schimmel H., Hawkins S. A., Moynagh J. other authors 2001; Rapid test for the preclinical post mortem diagnosis of BSE in central nervous system tissue. Vet Rec 149:577–582 [CrossRef]
    [Google Scholar]
  18. Gravenor M. B., Stallard N., Curnow R., McLean A. R. 2003; Repeated challenge with prion disease: the risk of infection and impact on incubation period. Proc Natl Acad Sci U S A 100:10960–10965 [CrossRef]
    [Google Scholar]
  19. Hawkins S. A. C., Wells G. A. H., Simmons M. M., Blamire I. W. H., Meek S. C., Harris P. 1997; The topographic distribution pattern of vacuolation in the central nervous system of cattle infected orally with Bovine Spongiform Encephalopathy. Bovine Pract 31:73–76
    [Google Scholar]
  20. Hawkins S., Wells G., Austin A., Ryder S., Dawson M., Blamire I., Simmons M. 2000; Comparative efficiencies of the bioassay of BSE infectivity in cattle and mice. In Proceedings of the Cambridge Healthtech Institute's 2nd International Transmissible Spongiform Encephalopathies Conference 2–3 October 2000 Alexandria, VA, USA:
    [Google Scholar]
  21. Henry C., Knight R. 2002; Clinical features of variant Creutzfeldt-Jakob disease. Rev Med Virol 12:143–150 [CrossRef]
    [Google Scholar]
  22. Hunter N., Goldmann W., Smith G., Hope J. 1994; Frequencies of PrP gene variants in healthy cattle and cattle with BSE in Scotland. Vet Rec 135:400–403 [CrossRef]
    [Google Scholar]
  23. Juling K., Schwarzenbacher H., Williams J. L., Fries R. 2006; A major genetic component of BSE susceptibility. BMC Biol 4:33–41 [CrossRef]
    [Google Scholar]
  24. Kimberlin R. H., Walker C. A. 1978; Pathogenesis of mouse scrapie: effect of route of inoculation on infectivity titres and dose response curves. J Comp Pathol 88:39–47 [CrossRef]
    [Google Scholar]
  25. Kimberlin R. H., Walker C. A. 1988; Incubation periods in six models of intraperitoneally injected scrapie depend mainly on the dynamics of agent replication within the nervous system and not the lymphoreticular system. J Gen Virol 69:2953–2960 [CrossRef]
    [Google Scholar]
  26. Kimberlin R. H., Walker C. A. 1989; Pathogenesis of scrapie in mice after intragastric infection. Virus Res 12:213–220 [CrossRef]
    [Google Scholar]
  27. Kimberlin R. H., Wilesmith J. W. 1994; Bovine spongiform encephalopathy. Epidemiology, low dose exposure and risks. Ann N Y Acad Sci 724:210–220 [CrossRef]
    [Google Scholar]
  28. Konold T., Bone G., Ryder S., Hawkins S. A. C., Courtin F., Berthelin-Baker C. 2004; Clinical findings in 78 suspected cases of bovine spongiform encephalopathy in Great Britain. Vet Rec 155:659–666 [CrossRef]
    [Google Scholar]
  29. McLean A. R., Bostock C. J. 2000; Scrapie infections initiated at varying doses: an analysis of 117 titration experiments. Philos Trans R Soc Lond B Biol Sci 355:1043–1050 [CrossRef]
    [Google Scholar]
  30. Outram G. W. 1976; The pathogenesis of scrapie in mice. In Slow Virus Diseases of Animals and Man . pp 325–357 Edited by Kimberlin R. H. Amsterdam: North-Holland Publishing Co;
  31. Prusiner S. B. 2004; An introduction to prion biology and diseases. In Prion Biology and Diseases pp 1–87 Edited by Prusiner S. B. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  32. Prusiner S. B., Cochran S. P., Groth D. F., Downey D. E., Bowman K. A., Martinez H. M. 1982; Measurement of the scrapie agent using an incubation time interval assay. Ann Neurol 11:353–358 [CrossRef]
    [Google Scholar]
  33. Prusiner S. B., Safar J., DeArmond S. J. 2004; Bioassay of prions. In Prion Biology and Diseases pp 143–186 Edited by Prusiner S. B. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  34. Robinson M. M., Cheevers W. P., Burger D., Gorham J. R. 1990; Organ-specific modification of the dose-response relationship of scrapie infectivity. J Infect Dis 161:783–786 [CrossRef]
    [Google Scholar]
  35. Simmons M. M., Harris P., Jeffrey M., Meek S. C., Blamire I. W. H., Wells G. A. H. 1996; BSE in Great Britain: consistency of the neurohistopathological findings in two random annual samples of clinically suspect cases. Vet Rec 138:175–177 [CrossRef]
    [Google Scholar]
  36. Stack M. 2004; Western immunoblotting techniques for the study of transmissible spongiform encephalopathies In Techniques in Prion Research . pp 97–116 Edited by Lehmann S., Grassi J. Basel: Birkhäuser Verlag;
  37. Taylor D. M., Fernie K., Steele P. J., Somerville R. A. 2001; Relative efficiency of transmitting bovine spongiform encephalopathy to RIII mice by the oral route. Vet Rec 148:345–346 [CrossRef]
    [Google Scholar]
  38. Terry L. A., Marsh S., Ryder S. J., Hawkins S. A. C., Wells G. A. H., Spencer Y. I. 2003; Detection of disease-specific PrP in the distal ileum of cattle exposed orally to the agent of bovine spongiform encephalopathy. Vet Rec 152:387–392 [CrossRef]
    [Google Scholar]
  39. Thackray A. M., Klein M. A., Aguzzi A., Bujdoso R. 2002; Chronic subclinical prion disease induced by low-dose inoculum. J Virol 76:2510–2517 [CrossRef]
    [Google Scholar]
  40. Wells G. A. H., Hawkins S. A. C. 2004; Animal models of transmissible bovine spongiform encephalopathies: experimental infection, observation and tissue collection. In Techniques in Prion Research pp 37–71 Edited by Lehmann S., Grassi J. Basel: Birkhäuser Verlag;
    [Google Scholar]
  41. Wells G. A. H., Simmons M. M. 1996; The essential lesion profile of bovine spongiform encephalopathy (BSE) in cattle is unaffected by breed or route of infection. Neuropathol Appl Neurobiol 22:453 (Abstract)
    [Google Scholar]
  42. Wells G. A. H., Wilesmith J. W. 1995; The neuropathology and epidemiology of bovine spongiform encephalopathy. Brain Pathol 5:91–103 [CrossRef]
    [Google Scholar]
  43. Wells G. A. H., Dawson M., Hawkins S. A. C., Austin A. R., Green R. B., Dexter I., Horigan M. W., Simmons M. M. 1996; Preliminary observations of experimental bovine spongiform encephalopathy. In Bovine Spongiform Encephalopathy – The BSE Dilemma pp 28–44 Edited by Gibbs C. J. Jr New York: Springer;
    [Google Scholar]
  44. Wells G. A. H., Hawkins S. A. C., Green R. B., Austin A. R., Dexter I., Spencer Y. I., Chaplin M. J., Stack M. J., Dawson M. 1998; Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet Rec 142:103–106 [CrossRef]
    [Google Scholar]
  45. Wells G. A. H., Spiropoulos J., Hawkins S. A. C., Ryder S. J. 2005; Pathogenesis of experimental bovine spongiform encephalopathy (BSE): pre-clinical infectivity in tonsil and observations on lingual tonsil in slaughtered cattle. Vet Rec 156:401–407 [CrossRef]
    [Google Scholar]
  46. Wilesmith J. W. 1991; The epidemiology of bovine spongiform encephalopathy. Semin Virol 2:239–245
    [Google Scholar]
  47. Wilesmith J. W., Wells G. A. H., Cranwell M. P., Ryan J. B. M. 1988; Bovine spongiform encephalopathy: epidemiological studies. Vet Rec 123:638–644
    [Google Scholar]
  48. Wilesmith J. W., Hoinville L. J., Ryan J. B. M., Sayers A. R. 1992a; Bovine spongiform encephalopathy: aspects of the clinical picture and analyses of possible changes 1986–1990. Vet Rec 130:197–201 [CrossRef]
    [Google Scholar]
  49. Wilesmith J. W., Ryan J. B. M., Hueston W. D. 1992b; Bovine spongiform encephalopathy: case control studies of calf feeding practices and meat and bone meal inclusion in proprietary concentrates. Res Vet Sci 52:325–331 [CrossRef]
    [Google Scholar]
  50. Will R. G., Ironside J. W., Zeidler M., Cousens S. N., Estibeiro K., Alperovitch A., Poser S., Pocchiari M., Hofman A., Smith P. G. 1996; A new variant Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925 [CrossRef]
    [Google Scholar]
  51. Zerr I., Poser S. 2002; Clinical diagnosis and differential diagnosis of CJD and vCJD. APMIS 110:88–98 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.82421-0
Loading
/content/journal/jgv/10.1099/vir.0.82421-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error